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Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 235 records · Page 13Linked to original sources

Characteristics of tissue distribution of various polysaccharides as drug carriers: influences of molecular weight and anionic charge on tumor targeting.

Using the Walker 256 model for carcinosarcoma-bearing rats, we intravenously administered 5 polysaccharide carriers with various molecular weights (MWs) and electric charges and tested for their plasma and tissue distribution. Two carriers, carboxymethylated-D-manno-D-glucan (CMMG) and CMdextran (CMDex), showed higher plasma AUC than the other carriers tested, namely, CMchitin (CMCh), N-desulfated N-acetylated heparin (DSH), and hyaluronic acid (HA). This was consistently found to be true over the range of MWs tested. For CMDex, the maximum value of plasma AUC was obtained when the MW exceeded 150 kDa. As for the anionic charge, CMDex (110-180 kDa) with a degree of substitution (DS) of the CM groups ranging from 0.2 to 0.6, showed maximum plasma AUC values. Twenty-four hours after administration, the concentration of CMDex (180-250 kDa; DS: 0.6-1.2) in tumors was more than 3% of dose/g--approximately 10-fold higher than those observed with CMCh, DSH and HA. Doxorubicin (DXR) was bound to these carriers via a peptide spacer, GlyGlyPheGly (GGFG), to give carrier-GGFG-DXR conjugates (DXR content: 4.2-7.0 (w/w)%), and the antitumor effects of these conjugates were tested with Walker 256 carcinosarcoma-bearing rats by monitoring the tumor weights after a single intravenous injection. Compared with free DXR, CMDex-GGFG-DXR and CMMG-GGFG-DXR conjugates significantly suppressed tumor growth, while the CMCh-GGFG-DXR, DSH-GGFG-DXR, and HA-GGFG-DXR conjugates in a similar comparison showed weak tumor growth inhibition. These findings suggest that the antitumor effect of the carrier-DXR conjugates was related to the extent with which the carriers accumulated in the tumors.

Animals↗

Cloning and characterization of a cDNA encoding beta-amyrin synthase involved in glycyrrhizin and soyasaponin biosyntheses in licorice.

An oxidosqualene cyclase cDNA, termed GgbAS1, was isolated from cultured cells of licorice (Glycyrrhiza glabra) by heterologous hybridization with cDNA of Arabidopsis thaliana LUP1 lupeol synthase. The yeast transformed with an expression vector containing the open reading frame of GgbAS1 produced beta-amyrin, indicating that GgbAS1 encodes beta-amyrin synthase involved in the glycyrrhizin and soyasaponin biosyntheses in licorice. Northern blot analysis showed that the level of beta-amyrin synthase mRNA was drastically changed in the cultured licorice cells, whereas the mRNA level of cycloartenol synthase was relatively constant.

Amino Acid Sequence↗

Glycosides of benzyl and salicyl alcohols from Alangium chinense.

From the water-soluble fraction of the dried leaves of Alangium chinense, three new glycosides, benzyl alcohol beta-D-glucopyranosyl-(1 --> 2)-[beta-D-xylopyranosyl-(1 --> 6)]-beta-D-glucopyranoside, 2'-O-beta-D-glucopyranosylsalicin, and 2'-O-beta-D-glucopyranosyl-6'-O-beta-D-xylopyranosylsalicin were isolated along with seven known glycosides. The structures of the new compounds were determined by spectroscopic and chemical means.

Benzyl Alcohols↗

Apoptosis induced by picolinic acid-related compounds in HL-60 cells.

We have found that niacin-related compounds, particularly picolinic acid, induced apoptosis in human leukemia cells. In this paper, we investigated whether various picolinic acid-related compounds had apoptosis-inducing activities or not. Particularly, fusaric acid, picolinaldehyde, nicotinaldehyde, 2-aminopyridine, and 3-aminopyridine also induced apoptosis in HL-60 cells. These results suggest that pyridine substituted with various groups and the consequent change of resonance structure may have an important role in the induction of apoptosis.

Apoptosis↗

Inhibition of Vero cell cytotoxic activity in Escherichia coli O157:H7 lysates by globotriaosylceramide, Gb3, from bovine milk.

In order to clarify the presence and verotoxin (VT) inhibitory activity of globotriaosylceramide (Gb3) in bovine milk, we analyzed neutral glycosphingolipids (GSLs) from bovine milk and investigated the inhibitory effect of bovine milk Gb3 on the cytotoxicity of VT2. Five species of neutral GSLs, designated as N-1, N-2, N-3, N-4, and N-5, were separated on thin-layer chromatography (TLC). N-1, N-2, and N-3 showed the same mobility as glucosylceramide, lactosylceramide, and Gb3 on the TLC plate, respectively. N-4 and N-5 GSLs migrated below globoside on the TLC plate. N-3 GSL having the same TLC mobility as Gb3 from bovine milk was immunologically identified as Gb3 by monoclonal antibody against Gb3, anti-CD77 monoclonal antibody. Furthermore, the effect of bovine milk Gb3 on VT2-induced cytotoxicity was investigated. We found that treatment of VT2 with bovine milk Gb3 can reduce the cytotoxic effect of VT2.

Adsorption↗

Increases of secondary metabolite production in various plant cell cultures by co-cultivation with cork.

Cork tissues increased secondary metabolite production of various plant cell cultures in a different manner from those of conventional elicitors. In Sophora flavescens and Glycyrrhiza glabra cultured cells, cork tissues increased the amounts of both lipophilic and hydrophilic flavonoids without affecting the cell growth, although elicitors such as copper ion and yeast extracts showed a clear inhibition of cell growth with the increasing amount of these lipophilic ones. The validity of this effect of cork tissues covered a wide range of aromatic compounds produced by suspension cell cultures derived from diverse plant species. Woody tissues of Japanese cypress had a very similar effect to that of cork. Partial purification of cork tissues suggested that the production-stimulating factor was present in the hemicellulose B fraction that was not included in the dedifferentiated cultured tissues.

Cell Wall↗

Adsorption effect of activated charcoal on enterohemorrhagic Escherichia coli.

The adsorption property of activated charcoal on verotoxin (VT)-producing Escherichia coli (VTEC) was examined using E. coli O157:H7. In the present study, E. coli O157:H7 strains were effectively adsorbed by activated charcoal. Adsorption was dose-dependent, and the maximum adsorption occurred within 5 min. At 10 mg of activated charcoal, bacteria tested were completely adsorbed. Activated charcoal also had the capacity to adsorb toxin (verotoxin 2) activity from the bacterial extract. Furthermore, the adsorption efficiency of activated charcoal for the normal bacterial flora in the intestine was assessed using Enterococcus faecium, Bifidobacterium thermophilum, and Lactobacillus acidophilus. Activated charcoal showed lower binding capacity to the normal bacterial flora tested than that to E. coli O157:H7 strains. These results suggest that activated charcoal could be a good adsorbent system for the removal of VTEC and verotoxin.

Adsorption↗

Atypical membranoproliferative glomerulonephritis in a cat.

Membranoproliferative glomerulonephritis was observed in a 2-year-old male Japanese domestic cat with clinical renal failure. In the glomeruli, moderate mesangial hypercellularity with an increased mesangial matrix and thickening of the capillary walls were prominent. In addition, frequent duplication of the capillary walls, splitting, and spike formation were observed in the glomerular basement membrane. Granular cat IgG and complement component deposition were detected globally along the glomerular capillary walls and in the mesangium. Transmission electron microscopy revealed dense deposits in the subendothelial and subepithelial regions and the mesangium. Mesangial interposition was also observed. These glomerular lesions are also found in humans with membranoproliferative glomerulonephritis type III, which has not been reported in animals.

Animals↗

Metastatic synovial sarcoma of the left ventricle.

A metastatic synovial sarcoma of the left ventricle is described. A 26-year-old Japanese woman underwent resection of a synovial sarcoma of the right thigh 8 years prior to admission, which was followed by multiple surgical procedures for pulmonary metastasectomy. Echocardiography demonstrated obstruction of the outflow tract of the left ventricle caused by a metastatic tumor, which was surgically resected on the day of admission. The histologic characteristics of the cardiac tumor were identical to those of the pulmonary metastases. Additional cardiac metastasectomy was performed 9 months later. She complained of dyspnea on exertion 8 months after the second cardiac metastasectomy due to recurrence in the heart. Radiotherapy with LINAC (a total dose: 50 Gy) diminished the size of the tumor temporarily. The patient died 20 months after the initial cardiac metastasectomy.

Adult↗

Different binding property of verotoxin-1 and verotoxin-2 against their glycolipid receptor, globotriaosylceramide.

We determined the binding of verotoxin-1 (VT1) and verotoxin-2 (VT2) against globotriaosylceramide (Gb3) by a monoclonal antibody (mAb)-based enzyme-linked immunosorbent assay (ELISA). Ethanolic solution of Gb3 containing cholesterol and phosphatidylcholine was passively adsorbed onto the wells of microtiter plate, and Gb3-bound VT1 and VT2 were detected by anti-VT1 and anti-VT2 mAbs, respectively. Although both VT1 and VT2 reacted with Gb3 in a concentration dependent manner, terminal galactose requirement for Gb3 binding was also different from each other. Pretreatment of VT1 showed the inhibitory effect on the binding of VT2 to Gb3, while the VT2-pretreatment showed no inhibitory effect on VT1 binding to Gb3. This was not due to the replacement of Gb3-bound VT2 with post-treated VT1. These results suggest that the binding sites of VT1 and VT2 on Gb3 are not identical to each other.

Animals↗

Expression of vascular endothelial growth factor in pulmonary aspergilloma.

OBJECTIVE: Vascular endothelial growth factor (VEGF), a cytokine associated with malignant neoplasms, is increased in a number of inflammatory and infectious disorders. But little is known about VEGF in pulmonary aspergilloma (PA). In order to clarify the predictive value of VEGF in PA, we examined serum VEGF levels in PA patients as well as expression of VEGF in the PA lesion. Patients Twenty-one patients with PA (6 with hemoptysis and the rest without hemoptysis) were investigated. METHODS: In all patients, serum VEGF levels were measured by enzyme-linked immunosorbent assay. We examined the statistical correlations of serum VEGF levels with the ratio of affected area to total lung volume and VEGF with PaO2 levels. In patients with hemoptysis, we measured the serum VEGF levels three months after the initiation of therapy. We examined the expression of VEGF in the resected lung tissue of 4 patients with PA using immunohistochemistry. RESULTS: Serum VEGF levels showed a significant positive correlation with the ratio of affected to total lung area and a significant negative correlation with PaO2 levels. Serum VEGF levels in patients with hemoptysis were significantly higher than in those without hemoptysis. The serum levels of VEGF in patients with hemoptysis decreased significantly in parallel with the alleviation of hemoptysis. Immunohistochemical staining demonstrated the expression of VEGF in alveolar macrophages in the lesion of PA patients. CONCLUSION: We suggest that VEGF can be used as a serum marker to determine the extent of the lesion, hypoxia and hemoptysis in PA.

Adult↗

Periodic lateralized epileptiform discharges in influenza B-associated encephalopathy.

An 18-year-old woman presented with coma, hemicomvulsions, and transient periodic lateralized epileptiform discharges (PLEDs). Serological tests were positive for influenza B, and cerebrospinal fluid PCR for herpes simplex virus DNA was negative. Magnetic resonance imaging later showed abnormal signal intensity in the temporal lobe ipsilateral to the PLEDs. Influenza-associated encephalopathy may cause hemiconvulsions and PLEDs, and can mimic herpes simplex encephalitis.

Adolescent↗

[Cause of bisphenol A migration from cans for drinks and assessment of improved cans].

In the previous investigation, we found that some cans for coffee and black tea drinks released large amounts of bisphenol A (BPA) into their contents. Equivalent cans were obtained and the cause of BPA migration was investigated. Equivalent cans A, B and D contained high levels of BPA in the side seam, in the bottom, and in the bottom and the side seam, respectively, while can C contained some level of BPA in the body, which has a large area, therefore, all of them contained high amounts of BPA in their coatings. In the migration test, there was no BPA migration from the cans into water at 60 and 95 degrees C for 30 min, into 20% ethanol at 60 degrees C for 30 min, or into n-heptane at 25 degrees C for 60 min. However, at 120 degrees C for 30 min, equivalent cans released 35-124 ng/mL BPA into the water. The total migration was similar to the total residues of BPA in the can coating and was close to the total amount of BPA in the drinks. Thus, BPA migration from the can coating requires heating to more than 105 degrees C, which is the glass transition temperature of the epoxy resin. Improved cans which contained less than 1/10 as much BPA as the equivalent cans showed very low migration levels, i.e., 3-6 ng/mL.

Benzhydryl Compounds↗

Early reduction in the aneuploidy at chromosomes 7 and 8 are significantly correlated with clinical effect in high-dose rate brachytherapy with external beam radiotherapy in localized prostate cancer.

Although reduction in the serum prostate specific antigen (PSA) correlates with clinical outcome for high dose rate Iridium-192 (HDR Ir-192) brachytherapy, it takes a long latency period. We investigated numerical chromosome changes of prostatic cancer during the pre- and post-treatment periods of HDR Ir-192 brachytherapy (and external beam radiotherapy), using fluorescence in situ hybridization (FISH) to clear the effect of treatment in early phase. Transitional changes in the frequency of aneuploidy for chromosomes 7, 8, 10, 12, 16, X, and Y in prostate cancer during the pre- and post-treatment periods were observed. Gains of chromosomes 7, 8 and 12 were noted in the pre-treatment samples (4 out of 12 cases in chromosomes 7 and 8; 1 out of 12 cases in chromosome 12), while a notable reduction in the number of cells with extra copies of these chromosomes was observed in post-treatment specimens. This change appears earlier than the reduction in the value of prostate specific antigen (PSA) and strongly reflects the effect of HDR brachytherapy with external beam radiotherapy in localized prostate cancer. Decrease in the number of cells with high ploidies of chromosomes 7, 8 and 12 at 12 weeks after treatment may predict clinical effects of radiation therapy, which may explain the radiation dependency of localized prostate cancer cells.

Aged↗